DE2855256C2 - - Google Patents

Description

The present invention relates to thiophosphorus acid esters of 5-hydroxypyrazoles, which are in position 1 and 3 are substituted; in particular, this relates Invention on the compounds mentioned, their preparation and their use as insecticides, Acaricides and nematicides.

The introduction of substituents into position 3 of the pyrazole Ringes prepares because of the special reactivity of the Pyrazolkernes some difficulties.

For example, pyrazoles, which are in position 3 through Halogen atoms are substituted, not by direct halogenation of the pyrazole nucleus, since the halogenation on the Position 4 takes place (see Tetrahedron 33, 1977, pp. 2069-2077).

To substitute the halogen in position 3 It is necessary to obtain the hydroxy group of the enol form of the Substituting pyrazol-3-ones with chlorinating agents.

The connections

have been produced accordingly: the first by Treatment of 3,5-dihydroxy-1-phenol-pyrazole with POCl₃ (see Reports 31, 1898, p. 3003); the second connection was made the former prepared by substitution of the chlorine atom (see Chemical Abstracts 60, 15880 a).

Recently, a process for the preparation of pyrazole which has been a substitution in position 3 or 5 with halogen (see "Tetrahedron" 33, 1977, p. 2069-2077).  

Phosphoric acid esters of heterocyclic enolisable compounds, including derivatives of 5- and 3-pyrazoles, are in the GB-PS 7 13 278 has been described; in it is among other things the Diethyl thiophosphoric acid ester of 3 (5) -methyl-5 (3) -hydroxypyrazole called. This connection is under the name "Pyrazothion" in trade.

From DE-OS 26 08 643 are O, S-dialkyl-thio-phosphoric acid ester of 1-cyanoalkylated 5-hydroxypyrazoles known have in the 3-position an alkyl or carbalkoxy radical. These compounds are effective as insecticidal and acaricidal described.

Furthermore, DE-OS 22 19 484, 20 60 198 and 20 37 853 (thio) phosphoric (phosphonic) acid esters of certain 3- or 5-hydroxypyrazoles and the use of these Compounds as insecticides and acaricides.

In DE-OS 23 37 293 there is a process for the preparation of 1-substituted 3-hydroxypyrazoles, of which indicated is that they as active ingredients, anti-inflammatory drugs and Intermediates for drugs of particular interest are.

The subject of the present invention is characterized by the above Claims defined.

According to the invention, the compounds of the general formula (I) from the corresponding unesterified 5-hydroxypyrazoles of general formula (II). The latter are z. B. accessible in the following ways:

• a) When X = halogen, a hydrazine R-NH-NH₂ (wherein R has the meaning given above), preferably in the form of a carbonyl derivative such as: (wherein R '= NH₂, OR³, R³ with R³ = alkyl)
  reacted with the chloride of a β- chloro- β- X-acrylic acid.
• The reaction product thus obtained is treated with an alkali base, whereby cyclization and simultaneously the elimination of the protective group he follows.
• In this way, the desired products are obtained in the form of alkali metal salts according to the following reactions:
• Acidification of the alkali metal salts gives the desired 5-hydroxy-pyrazoles.
• b) When X is a vinyl group (optionally substituted), the synthetic method is to react an ethyl acrylate of the formula: C₂H₅O-CO-CH₂-CO-C (Y) = CY₂ with a hydrazine which is optionally mono-substituted, according to the equation :

In the following Table 1, some representative Compounds of the above formula II and their properties are shown.  

Table 1

5-hydroxypyrazoles of the general formula II

The compounds according to the invention have great activity against numerous harmful insects, mites (Acari) and roundworms (Nematoda). This effectiveness is the well-known, chemically similar compounds, such as. Pyrazothion, superior and in some cases the latter has no effect from (see Table 3).

Compounds of general formula I can by Reacting a thiophosphoric acid halide with an alkali metal Salt of hydroxypyrazole (see Example 11) according to the following scheme are obtained:

(wherein R, R¹, R² and X have the same meanings as for Formula I, W = halogen and M⁺ = a Cation of an alkali metal.)

Particular embodiments of the compound of formula I are those in which R is phenyl or benzyl and X is chlorine, or R is alkyl of 1-7 C atoms and X is chlorine, or in wherein R¹ and R², which may be the same or different, are alkoxy R, H or alkyl having 1-7 C atoms, optionally substituted with CN groups, and X is chlorine.

The thiophosphoric acid esters of 5-hydroxypyrazoles, which in Table 2 have been described above prepared method described.  

Table 2

Thiophosphoric acid esters of 5-hydroxypyrazoles of the general formula I.

The compounds of the general formula I possess a remarkable effectiveness against insects such. B. Lepitoptera, Diptera, Coleoptera etc. as well as Acari and Nematoda.

The effectiveness as an insecticide by the in Example 12 is confirmed in the following Table 3 of the effectiveness of "Pyrazothion" contrasted.

It is clear from the data in Table 3 that the Compounds of the general formula I an activity those of the reference substance, in Blatta and Macrosiphum applied, is superior; also these are surprisingly effective against Spodoptera, Culex, Musca, Leptinotarsa, Meloidogine incognita, in which the Comparative substance proved ineffective.  

Table 3

Effectiveness of the compounds of the invention against insects, Acari and Nematoda using the indicated dosages, expressed as a percentage decrease in the infestation

The compounds of general formula I according to the invention moreover, another surprising Property favorable for use as insecticides is. They are in general with a relatively low Toxicity to mammals equipped with their Toxicity, as can be seen from Table 4, much lower than that of Pyrazothion.

Toxicity by ingestion in rats (mg / kg) Connection no. LD 50 2 155 1 400 4 800 6 175 Pyrazothion 36

The compounds according to the invention can according to the customary methods: as a powder, as a wettable Powders, solutions, emulsions or suspensions.

The following examples serve to further describe the invention, Examples 1 to 10 merely indicate the preparation of the intermediates of formula II.

Example 1 Preparation of 1-phenyl-3-chloro-5-hydroxypyrazole (Method a-1)

To a suspension of 7 g of 1-phenylsemicarbazide in 100 ml of acetonitrile cooled to 0-5 ° C was added 7.4 g of β, β- dichloroacryloyl chloride with stirring. After the addition, the reaction mixture was stirred for 30 minutes at 5 ° C and then for 1 hour at room temperature. The separated solid was collected by decantation and filtration and washed with diethyl ether. There was thus obtained 8 g of 1- ( β, β- dichloroacryloyl) -1-phenyl-semicarbazide, which was confirmed by elemental analysis, IR and NMR spectra.

After evaporation of the reaction mother liquor to dryness a solid residue was isolated after washing with diethyl ether gave a further 3 g of the same product.

To a 10% aqueous solution of NaOH (110 g), kept under stirring at a temperature between 55 ° C and 60 ° C, was added a small amount of 5.5 g of 1- ( β, β- dichloroacryloyl) - 1-phenylsemicarbazide added. After the addition, the solution was kept at 60 ° C for 10 minutes, then allowed to cool, diluted with 50 ml H₂O and poured the mixture dropwise into a slight excess of a dilute HCl solution. This formed a precipitate. The resulting mixture was extracted with diethyl ether (50 ml x 3) and the extract yielded, after evaporation of the solvent, 4 g of 1-phenyl-3-chloro-5-hydroxypyrazole.

The mass, NMR and IR spectra as well as the elemental analysis agreed with the assumed structure.

example 2 Preparation of 1-isopropyl-3-chloro-5-hydroxypyrazole (Method a-2)

To a solution of 5 g of 1-isopropyl-2-carbethoxyhydrazine was added 3 g of triethylamine and then, dropwise with stirring, 5.5 g of β, β- dichloroacryloyl chloride, maintaining the temperature between 0 and -5 ° C. After the addition, the chloroform solution was washed with a dilute aqueous solution of hydrochloric acid, dried with Na₂SO₄ and the solvent was finally evaporated, thereby obtaining 8.1 g of 1- ( β, β- dichloroacryloyl) -1-isopropyl-2-carbethoxyhydrazine. The elemental analysis confirmed the assumed structure.

5 g of this intermediate was added to a solution of 5 g NaOH in 10 ml H₂O at 60 ° C with stirring. Once the solution was clear, it was cooled to room temperature and then with Acidified with 10 ml of concentrated HCl. The separating one Solid was extracted with chloroform (3 x 50 ml). To Evaporation of the solvent gave 2.7 g of 1-isopropyl 3-chloro-5-hydroxypyrazole (m.p. 138-140 ° C).

The mass, NMR and IR spectra are elemental analysis confirmed the adopted structure.

Examples 3 to 5 (Method a-2)

Following the same procedure as described in Example 2 the following compounds were prepared, starting from the following hydrazine derivatives:

C₂H₅-NH-NH-COOC₂H₅ → 1-ethyl-3-chloro-5-hydroxypyrazole
H₂N-NH-COOC₂H₅ → 3-chloro-5-hydroxypyrazole
NC-CH₂-CH₂-NH-NH-COO₂H₅ → 1- (2-cyanoethyl) -3-chloro-5-hydroxypyrazole.

example 6 Preparation of 1-methyl-3- ( β, β -dichlorovinyl) -5-hydroxypyrazole (Method b)

To 2,1 g of ethyl β, β- dichloroacryloyl acetate in 10 ml of acetic acid were added 0.46 g of methylhydrazine with constant stirring. This reaction mixture was kept at 75 ° C for 1 hour and then at 110 ° C for 1 hour. Then the reaction mixture was allowed to cool and diluted with 60 ml of water. The solid, which precipitated gradually, was extracted with ethyl acetate. The extract was washed with an aqueous solution of NaHCO₃ and then the solvent was evaporated, yielding 1.5 g of 1-methyl-3- ( β, β -dichlorovinyl) -5-hydroxypyrazole (melting point = 210 ° C after washing with diethyl ether) ,

Examples 7 to 10 (Method b)

Following the same procedure as described in Example 6 the following compounds were prepared, starting from the following hydrazines:

H₂N-NH₂ → 3- ( β, β- dichlorovinyl) -5-hydroxypyrazole
i -C₃H₇-NH-NH₂ → 1-isopropyl-3- ( β, β -dichlorovinyl-5-hydroxypyrazole
NC-CH₂-CH₂-NH-NH₂ → 1- (2-cyanoethyl) -3- ( β, β -dichlorovinyl) -5-hydroxypyrazole
C₆H₅-NH-NH₂ → 1-phenyl-3- ( β, β -dichlorovinyl) -5-hydroxypyrazole.

Example No. 11 Preparation of 0,0-dimethyl-O- (1-phenyl-3-chloropyrazol-5-yl) thiophosphate

To 5 g of 1-phenyl-3-chloro-5-hydroxypyrazole in 120 ml of acetone were 5.3 g of K₂CO₃ and 4.12 g of 0,0-dimethyl-thiophosphoryl chloride added.  

This reaction mixture was stirred for 4 hours and then filtered to remove the inorganic salts. After evaporation of the solvent gave 8 g of 0,0-dimethyl-0- (1-phenyl-3-chloropyrazol-5-yl) thiophosphate in the form of an oil (Compound 1, Table 2).

All other compounds listed in Table 2 were made in the same way.

Example No. 12 Biological activity of Macrosiphum eupharbiae (aphids)

On small potato plants that have been grown in pots were adult female aphids (Aphididae) settled. After several hours, these were washed with a watery Sprayed dispersion of the test product.

The percentage mortality was 24 hours after treatment determined (untreated plants = 0).

Biological activity of Pieris brassicae (Lepitoptera)

Cutted cauliflower leaves were washed with an aqueous dispersion of Test product sprayed. After drying, 5 days old Larvae settled. The percentage mortality of the larvae (untreated leaves = 0) was given 48 hours after treatment detected.

Biological activity of Leptinotarsa decemlineata (Coleoptera)

On small, pot-grown potato plants were 4 days settled on old larvae and then with a watery solution the test product sprayed. The percentage mortality (untreated plants = 0) was 48 hours after the Treatment noted.

Biological activity of Culex pipiens larvae (Diptera)

In glasses containing an aqueous dispersion of the test product mosquito larvae of the L₃-L₄ stadiums given. The percentage mortality of the larvae (jars with  clear water = 0) was detected 24 hours after treatment.

Biological efficacy in adult Tetranychus urticae (Acari)

Small disc-shaped sections of bean leaves were added populated with adult mites and then with an aqueous Sprayed dispersion of the test product.

The percentage mortality was 24 hours after treatment determined (mortality for untreated leaves = 0).

Biological activity in Spodoptera littoralis (Lepidoptera)

Cut tobacco leaves were treated with an aqueous dispersion the test product sprayed. After drying, the Leaves colonized with 5 day old larvae.

The percentage mortality of the larvae was 48 hours after Treatment (mortality on untreated Scroll = 0).

Biological activity of Meloidogyne ingognita (Nematoda)

Proportions 1: 1 of a mixture of feldspar and sand were colonized with Nematoda larvae and eggs and with a aqueous dispersion of the test product treated by this was uniformly mixed. The earth was then in Plastic pots were distributed and after 5 days were in each pot 5 tomato plants - about 20 cm high - planted. 21 days after planting, a determination of the results was made, by taking the roots of the plants pulled from the earth examined the extent of infestation by counting the growths determine who had formed at this.

The efficacy of the nematocide was expressed as a percentage decrease of infestation with respect to the control plants (activity at small plants planted in untreated soil = 0) shown.

Biological activity in Blatta orientalis (Ortoptera)

The bottom and side walls of glass crystallizers were  treated uniformly with an acetone solution of the test product. After evaporation of the solvent in each crystallizer were in these 10 each 80-100 day old Neaniden (nymphs) used. The bowls were covered with a metal grid closed. 24 hours after the start of treatment, the Insects in the same crystallization vessels and transferred properly fed.

The percent mortality (untreated insect = 0) was 48 hours after the start of treatment.

Biological activity in Musca domestica (Diptera)

4 day old, mature insects were topically applied of the test product as acetone solution using a microsyringe treated.

The percent mortality (in insects that only with acetone were treated = 0) was detected 24 hours after treatment.

Biological efficacy in Culex pipiens - fully grown (Diptera)

"Whatman" paper No. 1 in the form of rectangles became uniform treated with an acetone solution of the test product. To Evaporation of the solvent became the inner wall of a plexi glastrichters (model OMS) with the treated paper rectangles designed. The cylinder was covered with a net after in these 2-3 days old, adult, female insects had been used. One hour after the start of the contact The insects were in a similar cylinder, in the same Way lined with untreated paper was transferred and fed with a sugar solution.

The percent mortality (untreated insect = 0) was 24 hours after the start of treatment.

Claims (3)

1. 5-hydroxypyrazole derivatives of the general formula I, wherein
R = H or alkyl of 1-7 carbon atoms, which is optionally substituted by CN, phenyl, 4-nitrophenyl or benzyl,
X = halogen or wherein the groups Y, which may be the same or different, represent H and halogen, and
R¹ and R², which may be identical or different, are alkyl or phenyl or an alkoxy or alkylamino group each having up to 3 C atoms. 2. A process for the preparation of the compounds according to claim 1, characterized in that corresponding 5-hydroxypyrazoles of the general formula II, in which R and X have the abovementioned meaning, treated with an alkali metal base in a polar solvent and the resulting alkali metal salt with a thiophosphonyl halide of the following general formula III, wherein R¹ and R² have the same meaning as in claim 1 and W is halogen , converts: 3. Agents for controlling insects, Acari and Nematoda, containing an effective amount of one or more Compounds according to claim 1.